Chlorination of 2-methoxynicotinic acid

Abstract

A novel process for chlorinating 2-methoxynicotinic acid at the 5-position of the molecule is disclosed. The process involves the use of an alkali metal hypochlorite as the chlorinating agent in a homogeneous aqueous solvent system. The compound so produced, 5-chloro-2-methoxynicotinic acid, is known to be useful as an intermediate leading to various oral hypoglycemic agents of the benzenesulfonylurea class.

I claim: 
     
       1. A process for chlorinating 2-methoxynicotinic acid at the 5-position of the molecule, which comprises subjecting said acid to the chlorinating activity of an alkali metal hypochlorite in a homogeneous aqueous solvent system at a temperature that is in the range of from about 10° C. up to about 30° C. until said chlorination reaction is substantially complete. 
     
     
       2. A process as claimed in claim 1 wherein the alkali metal hypochlorite employed as reagent is sodium hypochlorite. 
     
     
       3. A process as claimed in claim 1 wherein the molar ratio of the 2-methoxynicotinic acid starting material to the sodium hypochlorite reagent is in the range of from about 1.0:1.0 to about 1.0:6.0. 
     
     
       4. A process as claimed in claim 3 wherein said molar ratio is in the range of from about 1.0:1.2 to about 1.0:2.0. 
     
     
       5. A process as claimed in claim 1 wherein the reaction is conducted at room temperature for a period of at least about 16 hours. 
     
     
       6. A process as claimed in claim 1 wherein the 5-chloro-2-methoxynicotinic acid so produced is recovered from the reaction mixture.